Biomedical subjects

G Skopp

Publications and source records attributed to G Skopp.

47 records · Page 3Linked to original sources

PubMedDate not supplied

Morphine and morphine glucuronides in serum of heroin consumers and in heroin-related deaths determined by HPLC with native fluorescence detection.

A simple, rapid, and sensitive high-performance liquid chromatographic method for the simultaneous determination of serum morphine, morphine-6-glucuronide (M6G), and morphine-3-glucuronide (M3G) based on native fluorescence detection is described. For the extraction of drugs and their metabolites, 200 microL serum was applied to 50 mg of a commercially available octylsilan phase. After isocratic separation in two steps (6.5 min) by reversed phase, the compounds were determined at an excitation wavelength of 245 nm and an emission wavelength of 345 nm (the limit of detection was approximately 5 micrograms/L for each compound). The concentrations of morphine, M6G (with respect to its potential analgesic activity), and M3G were investigated in 20 heroin addicts in police custody and in 10 heroin-associated deaths. The ratios between M6G or M3G and the morphine concentrations and between M6G and M3G are related to the morphine concentration and consequently depend on the time elapsed since the last administration of morphine or heroin. Consequently, the M6G values were found to be higher in cases of death than in the living addicts. By considering the M6G/morphine or M3G/morphine ratios, the narcotic effect of heroin as reflected by morphine and its metabolite concentrations in impaired addicts and cases of fatal poisoning can be better assessed than by use of the morphine concentration alone.

Chromatography, High Pressure Liquid↗

PubMedDate not supplied

Plasma concentrations of heroin and morphine-related metabolites after intranasal and intramuscular administration.

The disposition of heroin and its metabolites was investigated in four healthy male volunteers following intranasal administration of 6 and 12 mg heroin hydrochloride. In addition, two doses of 6 mg heroin hydrochloride were injected intramuscularly for comparison of pharmacokinetic parameters. Serum samples were analyzed for heroin, 6-acetylmorphine, and morphine by solid-phase extraction-gas chromatography-mass spectrometry. The concentration of morphine glucuronides was determined by high-performance liquid chromatography based on the native fluorescence of the conjugates. Major findings were rapidly rising and declining terminal phases for heroin and 6-acetylmorphine and slowly declining phases of morphine and metabolites after both routes of administration. The area under the curve values of morphine-3-glucuronide depended on dose but not on route of administration. The apparent terminal half-lives of morphine-3-glucuronide ranged from 2.2 to 5.2 h for intranasally administered heroin and were 3.0 and 1.7 h for the intramuscularly applied drug. A mean morphine-3-glucuronide-heroin area-under-curve ratio of 93 for the intranasal route as compared with 38 for the intramuscular route demonstrated that circulating amounts of heroin were about half the size after intranasal administration of the same dose.

Administration, Intranasal↗

PubMedDate not supplied

A preliminary study on the distribution of morphine and its glucuronides in the subcompartments of blood.

The distribution of morphine, morphine-3-glucuronide (M3G), and morphine-6-glucuronide (M6G) in whole blood, plasma, and packed erythrocytes was studied. Parameters investigated were the hematocrit values (10, 42, 44, and 71%) and the water content of the samples. The blood-to-plasma ratio of morphine concentrations was unaffected by variations in hematocrit and water content, whereas the corresponding ratios for M3G and M6G were strongly influenced. Ratios were 0.53 to 0.65 and 0.52 to 0.62 in specimens with average hematocrit values (42 and 44%, respectively), and the ratios were 0.81 or 0.89 (hematocrit 10%) and 0.27 or 0.28 (hematocrit 71%) in blood samples with different hematocrit values. In contrast to the morphine conjugates, morphine was highly bound to or partitioned into red blood cells (beta e = 55.9). Although the present data are limited, they already demonstrate that conclusions drawn from pharmacokinetic studies and transferred to parent drug to metabolite ratios resulting from forensic blood samples may be biased by the particular biological matrix under investigation.

Centrifugation↗

PubMedDate not supplied

Stability of morphine, morphine-3-glucuronide, and morphine-6-glucuronide in fresh blood and plasma and postmortem blood samples.

The present study was designed to determine the stability of morphine and its glucuronides in spiked fresh blood and plasma from live individuals as well as in four authentic postmortem blood specimens for a time interval of up to six months. The samples were stored in glass vials at -20 degrees C, 4 degrees C, and 20 degrees C. Additionally, spiked samples were exposed to light through window glass and subjected to a forced-degradation study at 40 degrees C. Data were established using solid-phase extraction and high-performance liquid chromatography coupled to atmospheric pressure ionization mass spectrometry for isolation and quantitation, providing a sensitive and specific detection method for the parent drug in the presence of its glucuronide metabolites. Morphine and its glucuronide metabolites were found to be stable in both blood and plasma at 4 degrees C for the whole observation period. In postmortem blood the analytes were stable only when stored at -20 degrees C. The thermal decomposition of morphine and morphine-6-glucuronide in spiked blood and plasma could be interpreted using pseudo first-order kinetics. Photodegradation of morphine-3-glucuronide in plasma was consistent with a second-order reaction. In postmortem samples the degradation pattern differed completely from that observed in fresh blood and plasma. The elevated morphine levels observed were primarily due to postmortem hydrolysis of morphine glucuronides.

Drug Stability↗

PubMedDate not supplied

[Serotonin, 5-hydroxyindolylacetic acid and cholesterol content in blood, cerebrospinal fluid and brain areas for differentiation of suicidal from non-suicidal cause of death].

In the present study serotonin and its metabolite 5-hydroxyindoleacetic acid was investigated in the cerebrospinal fluid and in discrete brain areas of the left and right hemisphere collected from 34 bodies. Sixteen subjects were suicide victims, and 18 were matched as controls. Matching was done for gender, age, sex and cause of death. In suicide victims the concentration of 5-hydroxyindoleacetic acid in cerebrospinal fluid (occipital) was significantly decreased whereas there was no difference comparing the particular results established from the various brain areas. Nevertheless, there was a non-significant trend towards a higher concentration of serotonin in the thalamic area and towards a lower level in samples collected from the mesencephalon in suicide brains. In suicide subjects, the level of 5-hydroxyindoleacetic acid was often found to be increased in the hippocampus and to be decreased in the thalamus. A differentiation between suicide and homicide seems promising only on condition that the distribution of serotonin and metabolite concentrations in various brain areas is considered. The amount of total cholesterol in blood is suggested to be of limited value.

Adult↗

PubMedDate not supplied

[Distribution of morphine and morphine glucuronides in body tissue and fluids--postmortem findings in brief survival].

An intoxication following administration of morphine, tramadol and atracurium in a suicide case is reported. The route of administration and the amount of the particular drug were known from the investigation of the death scene and the findings of the postmortem examination. Tramadol was present in the gastric contents as well as in blood, liver, kidney and brain samples, whereas the drug could not be detected in muscle. All body fluids and tissues investigated contained morphine as well as its 3- and 6-glucuronides with the exception of muscle tissue. The concentrations of morphine and its glucuronide metabolites were determined by LC/MS following solid phase extraction. Interestingly, the concentration of M6G in brain, liver and kidney were close to the concentration of M3G in the particular tissue. This phenomenon might be explained by a preferential hydrolysis of M3G or by a preferential formation of M6G postmortem. Measurement of morphine and M6G in femoral blood and cerebrospinal fluid may be a useful indicator in rapid deaths.

Autopsy↗

PubMedDate not supplied

[Detection of cocaine in blood stains].

Cocaine is rapidly degraded in blood samples, and its degradation was found to be highly dynamic in nature. The analysis of blood spots dried on filter paper may provide a method to minimize the break-down of cocaine and to largely preserve the analytical profile of the parent drug and its hydrolysis products at the time of sampling. The short term stability of cocaine in 100 microL blood spots prepared from unpreserved and preserved (sodium fluoride, 0.25%) blood samples was compared to the stability of the particular whole blood specimens stored in tubes at ambient temperature and at -20 degrees C. Due to dehydration, both the chemical and the enzymatic hydrolysis of cocaine and its products could be stopped in dried blood spots. More than 75% of the initial cocaine concentration could be detected in the blood spots, and the analytical profile was ensured for 17 days. Provided its practical suitability, the spot technology should offer a simple approach to detect actual impairment of motorists taken in police custody in the view of section 24a of the German traffic act as well as in cocaine associated criminal cases.

Accidents, Traffic↗

PubMedDate not supplied

[Passive exposure in detection of low blood and urine cannabinoid concentrations].

Whenever small amounts of drugs are present in blood or urine samples, especially of substances that are preferentially smoked such as cannabinoids, the discrimination between active and passive inhalation may cause severe problems. The statement of a passive exposure by marijuana smoke has been scrutinized reviewing the literature. The pharmacokinetics of smoked marijuana as well as experimental data on cannabinoid concentrations in plasma and urine samples following passive exposure are summarized. As a conclusion it seems urgent to enlarge the existing data base.

Automobile Driving↗

PubMedDate not supplied

[Serum beta-glucuronidase activity in polytrauma patients and in centrifuged autopsy blood samples].

The serum activity of beta-glucuronidase was investigated in 58 patients after severe trauma as well as in 43 autopsy cases. In 10 cases the enzyme activities in postmortem blood samples from the femoral vein were compared to those present in the correspondent heart blood samples. An elevated activity of beta-glucuronidase was observed in 14% of the patients within the first 36 h after severe trauma increasing to 62% in blood samples collected later on. The activity of beta-glucuronidase in the heart blood samples was always higher than in the corresponding sample from the femoral vein. In cases of prolonged post-mortem interval an elevated activity might have been due to bacterial contamination. In postmortal blood samples from the femoral vein an elevated enzyme activity was found in 70% of the study material. The results of the preliminary study on the activity of beta-glucuronidase in blood samples frequent in forensic routine work indicated that an elevated enzyme activity might be present for the following scenery: after severe trauma, in alcohol/drug abuse, presence of putridity/autolysis, presence of inflammatory processes, in diabetes as well as in carcinoma diseases. The significance of elevated beta-glucuronidase activity concerning alterations of unconjugated drug concentration due to in vitro cleavage of O-glucuronides should be investigated.

Autopsy↗

PubMedDate not supplied

[Storage stability of flunitrazepam, flurazepam, diazepam and metabolites in blood and plasma].

The stability of flunitrazepam, flurazepam, diazepam and some of their metabolites in spiked blood and plasma samples was studied bei GC-ECD analysis at defined time intervals up to 240 days. Validation data of the method are given. The blood or plasma samples were stored either at 22 degrees C or at 4 degrees C, and were exposed to global natural light irradiation or protected from light. All substances considerably decreased during the time interval studied. Flunitrazepam soon disappeared completely at room temperature (22 degrees C), while diazepam and flurazepam proved to be more stable, but a clear pattern of breakdown could not be established. The data obtained suggest a result from a long-term stored sample to be cautiously interpreted. Further investigation concerning the stability of drugs and the establishment of optimal storage conditions seem necessary.

Anti-Anxiety Agents↗

PubMedDate not supplied

[Fatal poisoning with clozapine and perazine. A case report].

An intoxication following an apparent overdose of clozapine (Leponex) and perazine (Taxilan) is reported. There was a wide range of variation in postmortem blood and tissue concentrations of clozapine, desmethyclozapine and perazine. Clozapine/norclozapine blood and tissue ratios and perazine-pill-fragments in the gastric content could be used as a sign of suspected acute clozapine and perazine overdose.

Adult↗